A Phase 1 open-label, first-in-human, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of actinium-225-macropa-pelgifatamab (BAY3546828)in participants with advanced metastatic castration-resistant prostate cancer (mCRPC)

The study treatment actinium-225-macropa-pelgifatamab (also called 225Ac-pelgi or BAY 3546828) is a new type of treatment under development for patients with mCRPC who have already received available treatments or have few treatment options available. It works by binding to a protein on the surface of the cancer cells called prostate specific membrane antigen (PSMA). As it gives off a type of radioactivity that travels a very short distance, it kills the nearby (cancer) cells that express PSMA. Participants in this study will take the study treatment 225Ac-pelgi once in a period of 6 weeks called a cycle. Each participant will have 4 of these treatment cycles if the participant benefits from the treatment. Each participant will be in the study for up to nearly six years, including a first test (screening) phase of a maximum of 28 days, up to 12 months of treatment depending on the participant’s benefit, and a follow-up phase of 60 months after the end of treatment. In addition, a sub study during the dose escalation part will gather information on the distribution of the study treatment in the body, the proportion that binds to the cancer cells, and the resulting radiation at the tumor site. During the study, the study team will do physical examinations, check vital signs such as blood pressure, heart rate, and body temperature, take blood, and urine samples, examine heart health using echocardiogram and electrocardiogram, take tumour samples, track 225Ac-pelgi in the body using gamma imaging (only selected sites), check the tumour status using PET (positron emission tomography), CT (computed tomography) or MRI (magnetic resonance imaging) and bone scans, and ask questions about the impact of the disease on the participants’ wellbeing and activities of daily life (Eastern Cooperative Oncology Group Performance status.